S236: RANDOMIZED MULTICENTER PHASE III STUDY OF HAPLO VERSUS HLA-MATCHED UNRELATED DONOR (UD) ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (ALLO HSCT) FOR PATIENTS OLDER THAN 55 YEARS
Authors: S. Harbi, J.-M. Boher, E. Forcade, P. Chevallier, R. Peffault De Latour, F. Malard, S. Francois, A. Charbonnier, E. Hermet, C. E. Bulabois, A. Huynh, A. Berceanu, T. Cluzeau, M. T. Rubio, S. Furst, R. devillier, M. Mohty, D. Blaise
Journal: HemaSphere (2022)

Background: In most situations where allo HSCT is wished a matched sibling donor (MSD) is lacking. The respective advantages of alternative donor such as UD or HaploD are yet to be precisely assessed notably in older population including the search and identification process. Aims: We performed a prospective, multicenter, open-label, randomized controlled trial (NCT02623309) comparing Haplo versus UD search strategies for allo HSCT in pts with hematological malignancies older than 55 years after the absence of MSD was established. Methods: The primary objective was the comparison of Chronic Graft-versus-Host Disease-free and Relapse-free survival (cGRFS) from time of randomization. Conditioning was RIC based on fludarabine (150 mg/m2), IV busulfan (260 mg/m2) for haplo HSCT with the adjunction of thiotepa (5 mg/kg) for UD-HSCT. Pts receiving Haplo-SCT and UD-HSCT received GVHD prophylaxis based on HD-PTCy (100 mg/kg) and ATG (5 mg/kg), respectively. Additionnal prophylaxis consisted in CSA and mycophenolate mofetil for all patients (pts). Results: 108 pts were enrolled, and 106 pts were analyzed with a median follow-up of 27 (14-34) months. Median age was 65 years (55-70). Diseases were myeloid malignancies in 84 pts (79%). DRI was low, intermediate and high in 5(5%), 59(55%) and 42(40%),respectively. 55 and 51 pts were assigned to Haplo and UD group respectively. In case an alternative donor was not identified in due time, a search for another donor was allowed. Of the 106 pts, 77 (73%) pts proceeded to transplant (40 (73%) and 37 (73%) pts in Haplo and UD group respectively). Fifteen (27%) pts in Haplo group did not because of progression (n=9), patient contraindication (n=5), absence of donor (n=1). Likewise 14 (27%) pts in UD group were not transplanted because of progression (n=8), patient contraindication (n=6). Overall median time from randomization to allo-SCT was 76 (21-179) and 95 (37-310) days in haplo and UD group respectively (P=NS). Thity-one (56%) and 26 (51%) pts actually were transplanted according to randomization while 9 (16%) and 11 (22%) pts were transplanted from a UD or a HaploD in haplo and UD search group respectively. Median time from randomization to allo-SCT was 81 (21-288) when the initial desired donor was found and 117 (38-310) days when another donor type was to be searched (p=0,04). In an intent-to-treat analysis from date of randomization, 2-year GRFS, PFS and OS did not differ between the two groups (Haplo vs UD search group: 29% vs 37%, p=0.22; 45 vs 49 %, p=0.56; 50 vs 59%, p=0.47). Overall 42 and 35 pts were actually transplanted from a haploidentical and unrelated donor, respectively whatever the randomization arm. With a median follow up of 24 months after transplant 2-year GRFS and PFS from transplant did not differ between Haplo and UD HSCT: 40% vs 34%, p=0.66; 48%vs 45%, p=0.78). No statistical difference was documented for G2-4 aGVHD, severe cGVHD, NRM and relapse probabilities. Summary/Conclusion: This trial from alternative donor search initiation time-point establishes for the first time that the search for a HaploD or UD conduct to the same outcomes in older pts. However, although 77% of the patients can achieved a transplant with either strategies, only half of the original pts will receive a transplant from the prospected donor type. Outcomes being similar, this may invite to initially perform search for both type of donors to avoid delay with secondary searches.